Estrogens exert biological effects in numerous organs throughout the body. The role of estrogens in reproductive biology, the prevention of postmenopausal hot flashes, and the prevention of postmenopausal osteoporosis are well established. Many observational studies have suggested estrogens also reduce the risk of development of cardiovascular disease(1), at least in part by estrogens reducing LDL cholesterol levels and elevating HDL cholesterol levels(2,3). More recently, estrogens have been suggested to inhibit the development of colon cancer(4), inhibit the development of Alzheimer's disease(5), and inhibit development of cataracts (6). The multitude of estrogen responses matches the widespread distribution of estrogen receptors (ER) throughout numerous organs, with ERα expression highest in uterus, pituitary, kidney and adrenal gland and ERβ expression highest in ovary, uterus, bladder and lung(7). While various estrogens have been profiled for biological activity, little is known regarding the patterns of gene expression which are responsible for these diverse activities.
Thus, a need exists for the systemic analysis of the regulation by estrogen and/or other hormonal compositions of gene expression in various tissues and the identification of the plurality of differentially expressed genes. The identification of candidate agents that at least partially exert the same differential expression and development of pharmaceuticals and new treatment methods based on such agents is highly desirable. There also exists a need for methods of monitoring conditions and for diagnostic products, including gene chips and kits, which may be used in the above-described analyses.
The embodiments provided herein relate generally to a plurality of genes, particularly a plurality of genes that are modulated by estrogen and/or other hormonal compositions in various organs, such as the uterus, kidney and pituitary gland. Such differentially expressed genes are useful in screening assays to examine the effects of a candidate agent on the expression of genes that are responsive to estrogen. A candidate agent that induces, in a given tissue, a gene expression profile that exhibits one or more similarities to the gene expression profile of estrogen and/or other hormonal compositions, can be identified for possible use in pharmaceuticals. The invention also relates to the identification of estrogen responsive genes that are known to be associated with the inhibition of certain conditions, such as shock, post-menopausal calcium deficiencies, cardiovascular diseases, and conditions where there is decreased renal blood flow, such as those caused by diuretics or congestive heart failure.